Key Statistics

Global incidence: An estimated 843,000 new cases and 732,000 deaths worldwide in 2024. Liver cancer is the third leading cause of cancer death globally.

U.S. incidence: About 42,340 new cases of liver cancer will be diagnosed in 2026 and about 30,980 people will die of the disease.

Survival: In the U.S., the 5-year relative survival rate is 22%, rising to 37% when liver cancer is found before it has spread outside the liver.

Trend: Liver cancer rates in the U.S. have tripled over the past four decades.

What is the Liver’s Role in the Immune System?

The liver is best known for filtering blood and helping with digestion, but it is also an important lookout post for the immune system. Most of the blood that flows into the liver comes directly from the intestines through a large vein called the portal vein. This blood carries nutrients from food, but also bits of bacteria and other microbes that have crossed the gut lining. This makes the liver an important place where the immune system can catch threats before they reach the rest of the body.

To do this job, the liver is packed with immune cells:

• Kupffer cells: These are specialized macrophages, immune cells that engulf and destroy germs and debris. They line the liver’s blood vessels and act like security guards, removing bacteria and other particles from the blood as it passes through.
• Natural killer (NK) cells: These cells can find and kill virus-infected cells and cancer cells without first needing to learn what to look for. The liver contains many more NK cells than most other organs, making them an important part of the liver’s immune defenses.
• T cells: The liver has many specialized T cells that can respond quickly to signals from microbes and stressed cells, acting as an early line of defense.

The liver also supports the immune response throughout the body. During an infection or injury, the liver quickly ramps up production of proteins that help tag germs for destruction and fuel inflammation. Doctors can measure some of these proteins, such as C-reactive protein (CRP), in blood tests as a sign that something is wrong.

At the same time, the liver must avoid overreacting to the harmless food molecules and gut bacteria it encounters every day. This balance between defense and tolerance helps keep the body healthy, but it can also create openings that cancer cells exploit.

How Can Vaccines Prevent Liver Cancer?

One of the most powerful tools to prevent liver cancer is vaccination. Chronic infections with hepatitis B or C viruses cause at least 80% of liver cancers worldwide. The hepatitis B vaccine prevents infection by teaching the immune system to make protective antibodies against the virus. Vaccinating early is especially important for cancer prevention, because babies and young children who become infected are much more likely than adults to develop a lifelong (chronic) infection. That is why the World Health Organization (WHO) recommends that all babies receive the first dose of the vaccine within 24 hours of birth, followed by additional doses in the first months of life.

There is not yet a vaccine for hepatitis C, although researchers are working to develop one. Antiviral medicines can now cure most hepatitis C infections, which lowers the risk of liver cancer. People who already have cirrhosis can still develop liver cancer after a cure, however, and need regular checkups.

Immunology and Liver Cancer

Many liver cancers start with long-lasting inflammation, whether from viral infection, heavy alcohol use, or fatty liver disease. In chronic hepatitis B and C, much of the damage comes from the immune system itself, which keeps attacking infected liver cells but cannot fully clear the virus. Over time, this repeated damage and repair leads to scarring and genetic changes that can turn healthy cells into cancer cells. Once a tumor forms, the liver’s natural tendency to calm immune responses works against the body. Cancer cells can take advantage of this to hide from immune attack. For example, they can display “stop” signals, such as a protein called PD-L1, that switch off T cells, and they can attract other immune cells that hold back the attack

Immune checkpoint inhibitors are a type of cancer immunotherapy that release the “brakes” on cancer-fighting T cells, helping them to find and attack cancer cells that were “hiding.” For advanced liver cancer that cannot be removed with surgery, doctors often combine more than one checkpoint inhibitor. These combinations of immunotherapy have helped some patients live longer. However, many patients still do not respond to available immunotherapies, and researchers are working to understand why.

What’s Next for Liver Cancer?

Immunology research continues to look for ways to help more patients benefit from immunotherapy. Scientists are:

• Investigating if these immune checkpoint inhibitors can be helpful for earlier-stage liver cancers, by shrinking liver tumors and making surgery possible in some cases, or in lowering the risk of the liver cancer coming back if these drugs are given after surgery.
• Looking to identify specific biomarkers that could indicate to doctors whether a patient’s tumor would respond to certain immunotherapies or not.
• Evaluating the use of CAR-T cell therapy to treat liver cancers
• Developing cancer vaccines to train the immune system to recognize and fight proteins or genetic changes found on cancer cells. This is different from the hepatitis B vaccine, which prevents infection from the virus.